Retinal pigment epithelium (RPE), a single layer of sheet of cells present between the retina and choroid, is vital for the normal functioning of the retina. Many of the inflammatory, infectious and hereditary diseases of the retina are associated with the degeneration and /or dysfunction of RPE. We have developed human RPE cell culture system and used as a model to investigate the various roles of RPE in the pathophysiology of retinal disorders. We have focussed our attention on transforming growth factor-beta (TGF-b), since TGF-b is involved in retinal disorders of proliferative, inflammatory and infectious etiology. Elevated expression of TGF-b in vitreous, retina and RPE has been closely correlated with the retinal fibrosis and choroidal neovascularization. Furthermore, clinical studies indicated potential use of TGF-b for the treatment of macular holes. We have previously reported the regulation of TGF-b expression by inflammatory cytokines. IL-1 and TNF-a enhanced the secretion of both TGF-b1 and TGF-b2. Enhancement of TGF-b1 and inhibition of TGF-b2 expression and secretion by IFN-g was observed in RPE cells. The contrasting effects of IFN-g on TGF-b1 and TGF-b2 suggest differential roles of TGF-b1 and TGF-b2 in the inflammatory diseases of the retina. Choroidal neovascularization (CNV) is one of the major events in the age related macular degeneration (ARMD), a leading cause of visual impairment in the aged population. Since vascular endothelial growth factor (VEGF) is associated with CNV, we have examined the expression of VEGF in RPE. Of various cytokines tested, TGF-b was found to be the potent inducer of VEGF. The Secretion of VEGF was maximal at 1ng/ml concentration and is completely abolished by actinomycin-D and cyclohexamide, inhibitors of transcription and translation of mRNA respectively. RT-PCR analyses indicated the presence of 121,165 and 189 aa isoforms of VEGF in RPE, which are upregulated by TGF-b. Actinomycin-D significantly inhibited TGF-b induced VEGF mRNA expression suggesting the action of TGF-b at transcriptional level. By using specific inhibitors of signal transduction, we found that TGF-b transcriptionally activate VEGF through MAPK and smad2 and smad4 pathway. Regulation of the expression of VEGF by TGF-b strongly suggests an important role for TGF-b in CNV in ARMD.